Abstract: Patients with cancer experience significant pain and report pain to be their most distressing symptom. The incidence of moderate to severe pain in patients with cancer remains greater than 50%. Behavioral interventions for cancer pain have demonstrated efficacy in randomized clinical trials (RCT), yet continue to be clinically underutilized. Optimizing behavioral interventions for cancer pain by generating evidence on optimal dosage (i.e., number of sessions, skills taught), intervention sequencing, and personal characteristics related to dose-response can improve implementation of behavioral cancer pain interventions. We propose using a novel controlled clinical trial design, a sequential multiple assignment randomized trial (SMART), to examine response to differing doses of a behavioral cancer pain intervention (Pain Coping Skills Training [PCST]) and subsequent response-based adjustments to doses. Cancer patients with pain (N=327) will initially be randomized to receive either PCST-Full or PCST-Brief. Participants who do not respond (<30% pain reduction) to their initially assigned intervention will be re-randomized to receive either maintenance (i.e., booster sessions focused on problem solving and skills reinforcement) or an increased level of intervention (i.e., additional sessions, skills). Participants who respond (> 30% pain reduction) to their initially assigned intervention will be re-randomized to either a maintenance dose or no further treatment. The aims of the study are to: 1) provide comparative evidence of response to differing initial doses PCST; 2) provide comparative evidence of intervention dose sequences of PCST that adjust based on patient response; 3) determine patient characteristics that moderate responses to initial and secondary doses of PCST following each dose and at a 6-month follow up and derive an optimal adaptive treatment strategy for personalizing selection of initial and secondary interventions based on the patient characteristics; 4) evaluate whether using primary PCST doses and subsequent PCST doses based on primary response is a cost-effective and practical approach to PCST. Hypotheses are: 1) PCST-Full will produce a significantly greater reduction in pain compared to PCST-Brief; 2) specialized SMART analyses will compare unique PCST intervention sequences identifying sequences that produce greater reductions in pain; 3) patient characteristics (i.e., pain interference, cancer stage, pain catastrophizing) will moderate participant responses to the initial and secondary intervention doses and can be used to develop an optimal adaptive strategy for selecting intervention doses; 4) practicality of this approach to PCST delivery will be demonstrated by cost-effectiveness of the intervention and successful overall accrual, high subject retention, and high intervention protocol adherence. This project is significant because it will enhance our ability to provide cancer patients with behavioral cancer pain interventions that better match their needs and characteristics, ultimately improving implementation and reducing pain and suffering.